Reaction StereochemistryReaction Stereochemistry

A regioselective reaction: preferential formation of oneconstitutional isomer

A stereoselective reaction: preferential formation of a stereoisomer

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StereoselectivityStereoselectivityvs.vs.

SterospecificitySterospecificity

Chiral Acids-BasesChiral Acids-BasesDiastereomersDiastereomers

A stereospecific reaction: each stereoisomeric reactant produces a different stereoisomeric product or a different set of products

All stereospecific reactions are stereoselectiveNot all stereoselective reactions are stereospecific

Many reactions convert achiral Many reactions convert achiral reactants to chiral products.reactants to chiral products.

If all of the components of the starting state (reactants, catalysts, solvents, etc.) are achiral, any chiral products that will be formed are racemic mixtures."Optically inactive starting materials can't give optically "Optically inactive starting materials can't give optically active products." active products."

In order for a substance to be optically active, it must be chiral and one enantiomer must be present in greater amounts than the other.

Stereochemistry of Electrophilic Addition Reactions of Alkenes

Can you determine the absolute configuration of the product?

Addition reactions that form one asymmetric carbon:How much of each isomer forms?

50:

50:

Many biochemical reactions convertMany biochemical reactions convertan achiral reactant to a singlean achiral reactant to a singleenantiomer of a chiral productenantiomer of a chiral product

Reactions in living systems are catalyzed by enzymes, which are enantiomerically homogeneous.

The enzyme (catalyst), which is chiral and optically active, is part of the reacting system, so such reactions don't violate the generalization that "Optically inactive starting materials can't give "Optically inactive starting materials can't give optically active products."optically active products."

ExampleExample

fumarasefumarase

HH22OO

CC CC

HOHO22CC HH

COCO22HHHH

CC OHOH

HHHOHO22CC

HOHO22CCHCCH22

Fumaric acidFumaric acid ((SS)-(–)-Malic acid)-(–)-Malic acid

AchiralAchiral Single enantiomerSingle enantiomer

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Addition reactions that form an additional asymmetric carbon

A radical reaction intermediate

Addition reactions that form two asymmetric carbons

Stereochemistry of Hydrogen Addition (Syn Addition)

• What is the optical yield for the reaction?What is the optical yield for the reaction?

• Will the physical properties of the products be the same?Will the physical properties of the products be the same?

++

CHCH33

HH

CHCH33

HH

68%68% 32%32%

A stereoselective reactionA stereoselective reaction

CHCH33

CHCH22

HH

CHCH33

HH

CHCH33

HH

HH22

PtPt

No, diastereomers have different physical properties.No, diastereomers have different physical properties.

36%= Pure - Racemic36%= Pure - Racemic

Stereochemistry of Hydroboration–Oxidation

Syn addition, that is from the same side: either top or bottom.What is the distribution and relationship of the products?Enantiomers or Diastereomers?

50: 50

Enantiomers

Addition reactions that form a bromonium ion (anti addition)

Stereochemistry Vocabulary

pro-R-hydrogen

pro-S-hydrogen

Enantiotopic hydrogens have the same chemicalreactivity and cannot be distinguished by achiral agents,but they are NOT chemically equivalent toward chiral reagents (Most relevant in biochemistry/physiology.)

Diastereotopic hydrogens do not have the same reactivity with achiral reagents

Applying the Principle:Applying the Principle:

Resolution of EnantiomersResolution of Enantiomers

Separation of a racemic mixture into its two enantiomeric forms.

Resolution of a Racemic Mixture

(R)-acid (S)-acidenantiomers

(S)-base(R,S)-salt (S,S)-salt

diastereomers

(R,S)-salt (S,S)-salt

HCl HCl

(S)-baseH+

+(R)-acid

(S)-baseH+

+(S)-acid

enantiomersenantiomers

C(+)C(+)C(+)C(+) C(-)C(-)C(-)C(-)

StrategyStrategy

enantiomersenantiomers

C(+)C(+)C(+)C(+) C(-)C(-)C(-)C(-)

2P(+)2P(+)

C(+)C(+)P(+)C(+)C(+)P(+) C(-)C(-)P(+)C(-)C(-)P(+)

diastereomersdiastereomers

StrategyStrategy

enantiomersenantiomers

C(+)C(+)C(+)C(+) C(-)C(-)C(-)C(-)

2P(+)2P(+)

C(+)C(+)P(+)C(+)C(+)P(+) C(-)C(-)P(+)C(-)C(-)P(+)

diastereomersdiastereomers

C(+)C(+)P(+)C(+)C(+)P(+)

C(-)C(-)P(+)C(-)C(-)P(+)

StrategyStrategy

enantiomersenantiomers

C(+)C(+)C(+)C(+) C(-)C(-)C(-)C(-)

2P(+)2P(+)

C(+)C(+)P(+)C(+)C(+)P(+) C(-)C(-)P(+)C(-)C(-)P(+)

diastereomersdiastereomers

C(+)C(+)P(+)C(+)C(+)P(+)

C(-)C(-)P(+)C(-)C(-)P(+)

P(+)P(+)

P(+)P(+)

C(+)C(+)C(+)C(+)

C(-)C(-)C(-)C(-)

StrategyStrategy

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ResolvingResolvingRacemic MixturesRacemic Mixtures

Chiral Acids-BasesChiral Acids-BasesDiastereomersDiastereomers